The goal of this research program is to gain basic knowledge concerning the medial hypothalamic basis of long-term food intake control and body weight regulation. The working model is that the metabolic receptors which mediate long-term body energy balance regulation are located primarily in this part of the brain, and that the regulation is accomplished by the capacity of these receptors to parallel peripheral metabolic processes as opposed to merely sensing a regulatory factor in the bloodstream. The proposed work shall deal with three major issues. 1) Initially we will attempt to precisely define subareas within the hypothalamus that have a higher than normal capacity to store nutrients. Accordingly, retention of radioactivity in the hypothalamus after intragastric loads of 14C-d-glucose will be assessed by slicing the hypothalamus in three planes of space and then by means of triangulation determining the location of high retention foci. These observations will be supplemented by autoradiographic procedures. 2) We will measure the metabolic characteristics of medial hypothalamic tissue possessing high nutrient retention. Regional levels of glycogen will be measured under various nutritional states. The lipogenic capacity of the tissues will be assessed by comparing synthesis of lipids from carbon-1 and carbon-6 labeled 14C-d-glucose precursors. The in vitro oxygen consumption and 14CO2 evolution of the tissue will be assessed in animals under various metabolic conditions. 3) The functional properties of the tissue will be determined by close analysis of feeding behavior of rats that have been injected intrahypothalamically with various metabolic precursors, primarily glucose, and with specific inhibitors of intermediary metabolism such as malonate and 2, 4 dinitrophenol. More specifically, we will attempt to determine to what extent hypothalamic energy regulation is controlled by amino acids which can be derived from glucose metabolism through the Krebs cycle, such as glutamate and GABA.